Personalized Vaccines May One Day Prevent Skin Cancer Relapses

Vaccines personalized to fight patients’ specific tumors may be the future of cancer treatment. Researchers recently developed vaccines tailored to individuals that successfully fought off skin cancer tumors in two small studies.

Two papers published in Nature in July showed that personalized vaccines were able to get rid of tumors in most patients who were tested.

“They’re personalized because the content of each vaccine is completely determined and designed by the mutation characteristics of that patient’s very own tumor,” said Catherine Wu, a physician at Dana-Farber Cancer Institute in Boston, who led one of the studies. “That same vaccine would not work or be appropriate for another individual. It only works for that individual patient.”

The researchers chose to study melanoma, the most serious kind of skin cancer, because it has one of the highest mutation rates of cancers. Both research teams used computational algorithms to detect and predict melanoma mutations.

These vaccines are a form of immunotherapy, which work by stimulating the immune system to attack cancer. While research in immunotherapy has shown promising results, doctors have found it also can pose serious risks to healthy organs, such as diabetes and severe reactions from immunotherapy drugs.

The vaccine that Wu’s team developed aimed to expand the number of T-cells targeting the cancer, personalizing it so that the T-cells target the specific makeup of the patients’ tumors. T-cells are a type of white blood cell that play an important part in our immune systems. This vaccine helped keep the cancer in check.

The team tested the vaccine on six patients whose tumors had been removed surgically, but were at risk of them growing back. Four of the six vaccinated patients had no cancer recurrence more than two years after the vaccination.

While the other two patients relapsed, their tumors regressed once they were treated with a PD-1 checkpoint inhibitor, a type of immunotherapy that blocks the shield that protects tumors from the immune system. The results show that these vaccines are effective both by themselves and when combined with other types of immunotherapy.

In the other study, led by Ugur Sahin, oncologist at the University Medical Center of Johannes Gutenberg University in Germany, the team created a personalized vaccine based on RNA, which converts the information stored in DNA to proteins.

Eight patients were tumor-free more than a year after treatment. Five other patients’ tumors had already spread by the time they received the vaccine. One patient became tumor-free after receiving a PD-1 inhibitor, and two patients’ tumors shrank, although the tumors resurged in one of them.

“If you compare the tumors of one patient to another, the overlap between two patients is extremely small,” Sahin said. “We decided if every patient has a different set of tumors, we can make a vaccine tailored to each patient.“

These vaccines, as with many other types of therapy, would be more effective in early stages of cancer. If the vaccine is eventually approved for use, doctors would have to produce the treatment quickly.

“The main challenge is every patient will get their own vaccination,” Sahin said. “This type of vaccination has to be done just in time. We have to really shorten the process. ... If approved, we would get thousands or ten thousands of patients a year. We need a system to deliver to thousands of patients.”

One challenge is cost, currently an estimated $50,000 to $100,000. Automation and digital solutions, Sahin said, could rapidly make the price more affordable as standard treatment.

The teams took about three months to produce these vaccines, although Wu predicted the process can be shortened to six weeks.

“Six weeks we think is acceptable in most cancer patients because they can get an operation or other conventional treatment with chemotherapy or a checkpoint blocker before the vaccine is ready,” said Cornelius Melief, emeritus professor at the Leiden University Medical Centre in the Netherlands, who reviewed the papers and wrote a commentary about them. “The vaccine should preferably be given as a combination treatment to take care of immunosuppressive mechanisms.”

Personalized vaccines also could work against other types of cancer. The algorithms for developing the vaccines are most effective for tumors with a high number of mutations, like skin cancer.

“That’s not true of the majority of cancers,” Wu said. “They don’t have the same number of high-level [mutations]. It’s our hope that as algorithms improve, we hope we can extend the benefit of this approach. All cancers do have mutations. If we can apply that approach, there is some degree of likelihood to generate some degree of immune response.”

Some aspects of the approach are ready to be tested other cancer types, Wu said, and the team is improving the sensitivity of predicting tumors.

The research teams plan to continue strengthening the vaccine and applying it to other types of cancer, as well as combining it with other types of immunotherapy to test the most effective ways to fight tumors.

Melief predicted that if the vaccine alone is insufficient, additional treatments can shrink tumors. The next step is conducting randomized studies on a larger number of patients.

“I think we will for a very long period of time not see any immunotherapy that can cure all patients, just like we have no targeted compounds and no chemotherapy or even therapy that can cure all patients,” Melief said. “There always remain escapes from the therapy, but what the two studies show are that cancer vaccines actually work. I think in the future it will be a game-changer, because vaccines are less expensive than many of the other types of cancer immunotherapy.”